Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts

Despite recent progress in its treatment, Multiple Myeloma (MM) remains incurable and its associated bone disease persists even after complete remission. Thus, identification of new therapeutic agents that simultaneously suppress MM growth and protect bone is an unmet need. Herein, we examined the effects of Aplidin, a novel anti-cancer marine-derived compound, on MM and bone cells. In vitro, Aplidin potently inhibited MM cell growth and induced apoptosis, effects that were enhanced by dexamethasone (Dex) and bortezomib (Btz). Aplidin modestly reduced osteocyte/osteoblast viability and decreased osteoblast mineralization, effects that were enhanced by Dex and partially prevented by Btz. Further, Aplidin markedly decreased osteoclast precursor numbers and differentiation, and reduced mature osteoclast number and resorption activity. Moreover, Aplidin reduced Dex-induced osteoclast differentiation and further decreased osteoclast number when combined with Btz. Lastly, Aplidin alone, or suboptimal doses of Aplidin combined with Dex or Btz, decreased tumor growth and bone resorption in ex vivo bone organ cultures that reproduce the 3D-organization and the cellular diversity of the MM/bone marrow niche. These results demonstrate that Aplidin has potent anti-myeloma and anti-resorptive properties, and enhances proteasome inhibitors blockade of MM growth and bone destruction

Swift detection of the super-swift switch-on of the super-soft phase in nova V745 Sco (2014)

V745 Sco is a recurrent nova, with the most recent eruption occurring in February 2014. V745 Sco was first observed by Swift a mere 3.7 hr after the announcement of the optical discovery, with the super-soft X-ray emission being detected around four days later and lasting for only ~two days, making it both the fastest follow-up of a nova by Swift and the earliest switch-on of super-soft emission yet detected. Such an early switch-on time suggests a combination of a very high velocity outflow and low ejected mass and, together with the high effective temperature reached by the super-soft emission, a high mass white dwarf (>1.3 M_sun). The X-ray spectral evolution was followed from an early epoch where shocked emission was evident, through the entirety of the super-soft phase, showing evolving column density, emission lines, absorption edges and thermal continuum temperature. UV grism data were also obtained throughout the super-soft interval, with the spectra showing mainly emission lines from lower ionization transitions and the Balmer continuum in emission. V745 Sco is compared with both V2491 Cyg (another nova with a very short super-soft phase) and M31N 2008-12a (the most rapidly recurring nova yet discovered). The longer recurrence time compared to M31N 2008-12a could be due to a lower mass accretion rate, although inclination of the system may also play a part. Nova V745 Sco (2014) revealed the fastest evolving super-soft source phase yet discovered, providing a detailed and informative dataset for study.Comment: 14 pages, 11 figures (4 in colour), accepted for publication in MNRA

Supersymmetry Breaking through Transparent Extra Dimensions

We propose a new framework for mediating supersymmetry breaking through an extra dimension. It predicts positive scalar masses and solves the supersymmetric flavor problem. Supersymmetry breaks on a ``source'' brane that is spatially separated from a parallel brane on which the standard model matter fields and their superpartners live. The gauge and gaugino fields propagate in the bulk, the latter receiving a supersymmetry breaking mass from direct couplings to the source brane. Scalar masses are suppressed at the high scale but are generated via the renormalization group. We briefly discuss the spectrum and collider signals for a range of compactification scales.Comment: 20 page

Are the magnetic fields of millisecond pulsars ~ 10^8 G?

It is generally assumed that the magnetic fields of millisecond pulsars (MSPs) are $\sim 10^{8}$G. We argue that this may not be true and the fields may be appreciably greater. We present six evidences for this: (1) The $\sim 10^{8}$ G field estimate is based on magnetic dipole emission losses which is shown to be questionable; (2) The MSPs in low mass X-ray binaries (LMXBs) are claimed to have $< 10^{11}$ G on the basis of a Rayleygh-Taylor instability accretion argument. We show that the accretion argument is questionable and the upper limit $10^{11}$ G may be much higher; (3) Low magnetic field neutron stars have difficulty being produced in LMXBs; (4) MSPs may still be accreting indicating a much higher magnetic field; (5) The data that predict $\sim 10^{8}$ G for MSPs also predict ages on the order of, and greater than, ten billion years, which is much greater than normal pulsars. If the predicted ages are wrong, most likely the predicted $\sim 10^{8}$ G fields of MSPs are wrong; (6) When magnetic fields are measured directly with cyclotron lines in X-ray binaries, fields $\gg 10^{8}$ G are indicated. Other scenarios should be investigated. One such scenario is the following. Over 85% of MSPs are confirmed members of a binary. It is possible that all MSPs are in large separation binaries having magnetic fields $> 10^{8}$ G with their magnetic dipole emission being balanced by low level accretion from their companions.Comment: 16 pages, accept for publication in Astrophysics and Space Scienc

Time of arrival through interacting environments: Tunneling processes

We discuss the propagation of wave packets through interacting environments. Such environments generally modify the dispersion relation or shape of the wave function. To study such effects in detail, we define the distribution function P_{X}(T), which describes the arrival time T of a packet at a detector located at point X. We calculate P_{X}(T) for wave packets traveling through a tunneling barrier and find that our results actually explain recent experiments. We compare our results with Nelson's stochastic interpretation of quantum mechanics and resolve a paradox previously apparent in Nelson's viewpoint about the tunneling time.Comment: Latex 19 pages, 11 eps figures, title modified, comments and references added, final versio

A comparative study of disc-planet interaction

We perform numerical simulations of a disc-planet system using various grid-based and smoothed particle hydrodynamics (SPH) codes. The tests are run for a simple setup where Jupiter and Neptune mass planets on a circular orbit open a gap in a protoplanetary disc during a few hundred orbital periods. We compare the surface density contours, potential vorticity and smoothed radial profiles at several times. The disc mass and gravitational torque time evolution are analyzed with high temporal resolution. There is overall consistency between the codes. The density profiles agree within about 5% for the Eulerian simulations while the SPH results predict the correct shape of the gap although have less resolution in the low density regions and weaker planetary wakes. The disc masses after 200 orbital periods agree within 10%. The spread is larger in the tidal torques acting on the planet which agree within a factor 2 at the end of the simulation. In the Neptune case the dispersion in the torques is greater than for Jupiter, possibly owing to the contribution from the not completely cleared region close to the planet.Comment: 32 pages, accepted for publication in MNRA

X-ray spectral properties of Seyfert galaxies and the unification scheme

Aims: The unification scheme of Seyfert galaxies predicts that the observed differences between type 1 and type 2 Seyfert galaxies are solely due to the differing orientations of the toroidal-shaped obscuring material around AGN. The observed X-ray spectra of Seyfert type 2s compared to type 1s are expected to be affected by higher absorbing column density due to the edge-on view of the obscuring torus. We study the 0.5 - 10 keV X-ray spectral properties of Seyfert type 1s and type 2s with the aim to test the predictions of Seyfert unification scheme in the X-ray regime. Methods: We use an optically selected Seyfert sample in which type 1s and type 2s have matched distributions in the orientation independent parameters of AGN and host galaxy. Results: The 0.5 - 10 keV XMM-Newton pn X-ray spectra of Seyfert galaxies are in general best fitted with a model consists of an absorbed power-law, a narrow Gaussian fitted to the Fe K{\alpha} emission line and an often seen soft excess component characterized by either a thermal plasma model with temperature kT \sim 0.1 - 1.0 keV and/or a steep power-law. The 2.0 - 10 keV hard X-ray continuum emission in several Seyfert type 2s is reflection dominated and suggests the Compton-thick obscuration. Results on the statistical comparison of the distributions of the observed X-ray luminosities in the soft (0.5 - 2.0 keV) and hard (2.0 - 10.0 keV) bands, the X-ray absorbing column densities, the equivalent widths of Fe K{\alpha} line and the flux ratios of hard X-ray to [OIII] {\lambda}5007{\AA} for the two Seyfert subtypes are consistent with the obscuration and orientation based unification scheme.Comment: 15 pages, 3 figures, 6 tables, accepted for publication in A&

Strong coupling, discrete symmetry and flavour

We show how two principles - strong coupling and discrete symmetry - can work together to generate the flavour structure of the Standard Model. We propose that in the UV the full theory has a discrete flavour symmetry, typically only associated with tribimaximal mixing in the neutrino sector. Hierarchies in the particle masses and mixing matrices then emerge from multiple strongly coupled sectors that break this symmetry. This allows for a realistic flavour structure, even in models built around an underlying grand unified theory. We use two different techniques to understand the strongly coupled physics: confinement in N=1 supersymmetry and the AdS/CFT correspondence. Both approaches yield equivalent results and can be represented in a clear, graphical way where the flavour symmetry is realised geometrically.Comment: 31 pages, 5 figures, updated references and figure